Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following spinal cord transection there occurred decreases in Km and Vmax of glutamate decarboxylase (GAD) both above and below the lesion, and an initial decrease in the concentration of GABA. Concomitantly, there was a gradual decrease in presynaptic inhibition. Eight to 12 weeks after spinal cord transection, Km and Vmax for GAD returned to control values, but the GABA content of the spinal cord below the lesion increased significantly and presynaptic inhibition became maximally depressed. These results suggested that during the chronic phase of spinal cord injury there is a decrease in release of GABA, the interneuronal inhibitory neurotransmitter which mediates presynaptic inhibition. Diazepam, a GABA enhancer, increased presynaptic inhibition in acute and chronic spinal cats, this being accompanied by a reduction in somatic muscular spasticity. The degree of this enhancement by diazepam, however, is attenuated with gradual loss of presynaptic inhibition. In the acute cat, a conditioning volley applied to cutaneous afferents blocked the inhibition of the monosynaptic response to extensor motoneurones. In contrast, in chronic spinal cats (eight to 12 weeks), the duration of complete blockade was markedly reduced and was followed by a prolonged period which cutaneous nerve stimulation potentiated the monosynaptic discharge. Similar to GABA, there also occurred an increase of substance P below the level of the lesion. Other neurotransmitters (e.g., norepinephrine, serotonin) accumulated above and disappeared below the transection level. Although somatic msucular spasticity appears to be, to some extent, due to GABA dysfunction in the spinal cord, alterations in "normal" functioning of other neurotransmitters and the loss of supraspinal control also contribute to this state.
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PMID:Correlation of changes in the GABA-ergic system with the development of spasticity in paraplegic cats. 51 79

Dantrium and Valium were compared in 22 children manifesting various degrees of spasticity. Treatment brought definite improvement in spasticity and in activities of daily living in 20 of the 22 patients. The two-part double-blind study showed that Dantrium was most effective in nine and Valium in seven cases. In four cases the drugs appeared to be equally beneficial. The combination of Dantrium and Valium appeared to be more effective in eight patients than either medication along, the greatest effect being seen in the upper extremities and about the hip joints. Patients on placebo showed no significant change. Side effects of lethargy and drowsiness on the combination were not bothersome after a short period of acclimation. The results indicate that the spasticity of cerebral palsy can be relieved significantly, and that the combination of peripherally and centrally acting agents is more beneficial than either medication alone.
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PMID:Medical treatment for spasticity in children with cerebral palsy. 79 60

The direct effect of diazepam on skeletal muscle has been examined in 15 patients with neurological lesions resulting in spasticity. Diazepam 15-30 mg. IV reduced the amplitude of the compound action potential of the direct muscle response (M response) and the isometric twitch tension. It is postulated that diazepam may affect the contractile properties of muscle and, possibly, the electrical properties of the muscle membrane. These peripheral effects may contribute to the reported clinical benefits of the drug in patients with spasticity including those patients with complete spinal lesions.
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PMID:Effect of diazepam on muscle contraction in spasticity. 96 32

Spasticity is a hyper-excitable state of the reflex arcs in the spinal cord below the level of injury. Not only is the skeletal motor system affected, but bladder, bowel, blood pressure, and erection reflex mechanisms are also involved. Spasticity gradually emerges from the initial phase of spinal shock one to two months after the injury, and usually reaches a plateau of a mild to moderate degree in 3 to 4 months. Neurophysiological mechanisms indicate an increase in the alpha and gamma reflex systems and that central excitability through the interneurons is also involved in these systems. Excessive spasticity should be recognized as a substitute for pain in the spinal cord injured patient, as infections, calculi, pressure ulcers, and other normally painful conditions set off the hyper-sensitive reflexes causing more spasticity. Education and health maintenance is the best prevention of severe spasticity. Definitive treatment of incapacitating spasticity is to find and treat the underlying disease condition, as well as to introduce medication which will also suppress the spasm (Valium and/or Dantrolene). Muscle motor points and/or nerve blocks with neurolytic agents is perhaps the best technique for quietening excessive spasticity. Intrathecal neurolytic agents, anterior or posterior rhizotomies and cordectomies are not advocated even in severe incapacitating spasticity as they are too destructive. Selective longitudinal myelotomy is by far the best surgical technique for disrupting excessive spasticity, if any such procedure is to be done. Tendonotomies may be necessary in chronic contractures of joints after the muscle spasticity has been reduced. Excessive spasticity is not regarded as a normal state in the spinal cord injured patient. The cause should be sought and treated. Nerve destruction techniques should not be used unless medical and nursing techniques have failed. Prevention is so important and can be achieved by education, health maintenance, and especially motivation.
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PMID:Spasticity following spinal cord injury. 119 52

The author gives a literature review of the management of spasticity carried out. Physical agents used such as ice, heat and vibration are described. Methods used by physical therapists are discussed. Drugs most commonly used in the treatment of spasticity are Diazepam, Baclofen and Dantrolene. Phenol has been used by injection into motor points, peripheral nerves and intrathecally. Other drugs that have been used are also discussed. Neurosurgical procedures include neurectomies, neurotomies, rhizotomies and more radical procedures such as myelotomies and cordectomies. Orthopaedic procedures involve muscle and tendon lengthening, release of contractures and tendon transfers. Surgery is discussed in terms of function. In considering the options, available care must be taken to achieve and maintain optimal functional level.
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PMID:The management of spasticity--a review of options available in rehabilitation. 129 22

The dihydropyridine Bay K 8644 exerts a positive modulation of Ca2+ channels. Administration of Bay K 8644 3-5 mg/kg i.p. to rats induces within 15 min a severe spasticity syndrome consisting of stiff tail, arched back, stretching and twisting of forelimbs and hindlegs and backwards motility and rolling over. The syndrome was effectively antagonized by nifedipine 3-30 mg/kg but not by the other Ca2+ channel blockers flunarizine, diltiazem and verapamil. Diltiazem even enhanced the spasticity. Diazepam 10-30 mg/kg i.p. completely blocked the spasticity whereas the other muscle relaxants (-)-baclofen and the beta-carboline ZK 93423 were completely inactive. These findings with Bay K 8644 suggest that spasticity may be caused by changed Ca2+ homeostasis.
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PMID:Bay K 8644 induces a reversible spasticity-like syndrome in rats. 243 19

The effects of conditioning stimulation of a mixed nerve in the leg, the common peroneal nerve (CPN), on the ipsilateral soleus H-reflex were compared with the effects of stimulating its cutaneous branch, the superficial peroneal nerve (SPN), in two groups of subjects--normals and patients with spinal spasticity subsequent to a clinically complete transection of the spinal cord. Condition-test delays of 20 msec to 2 sec, measured from the end of the 20 msec train (3 pulses at 100 Hz), were investigated. In normal subjects, CPN stimulation at 1.4 X MT profoundly depressed the soleus H-reflex. There was an initial depression (peak 40-90 msec) followed by a slow recovery which was incomplete at condition-test delays of 2 sec. One-half of the subjects showed a late facilitation, or disinhibition, peaking at 170-190 msec. The inhibitory effects were attributed to activation of low threshold, groups I and II, muscle afferents because stimulation of the SPN, at 1.5 X threshold for a compound action potential recorded from the CPN, had only facilitatory effects on the soleus H-reflex. Facilitation occurred at condition-test delays of 30-190 msec. The cutaneous stimulation was presumed to activate the largest, A beta, cutaneous afferents as it elicited a weak paraesthesia on the dorsum of the foot. The results suggested that cutaneous afferents may have contributed to the late facilitation seen with CPN conditioning stimulation. In spinal cord-lesioned subjects, CPN stimulation depressed the soleus H-reflex but the decrease was less and the recovery was faster and more complete than in normals. The magnitude of the initial depression at 20-100 msec varied with the severity of the spasticity, subjects with mild spasticity showing less of a depression. Weak cutaneous conditioning stimulation either had no effect or produced a slight depression of the soleus H-reflex, providing clear evidence that transmission in the pathways mediating the facilitatory effects of cutaneous afferents onto extensor motoneuronal pools is depressed in spinal spasticity. This may shift the balance of activity toward the flexor motoneurones, thus favouring the development of, for example, flexor spasms and flexor hypertonia. Since inhibitory effects from cutaneous stimulation are associated with activation of higher threshold afferents in normal man, the present results may reflect a decrease in the threshold for flexor withdrawal reflexes commonly associated with spasticity of spinal origin.
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PMID:Inhibitory and facilitatory effects from the peroneal nerve onto the soleus H-reflex in normal and spinal man. 244 16

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.
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PMID:Treatment of spasticity with tizanidine in multiple sclerosis. 367 23

Centrally acting muscle relaxant properties of AD-2239 were compared with those of tolperisone, eperisone, diazepam and baclofen. AD-2239 dose-relatedly depressed extensor reflex in urethane-chloralose anesthetized intact and spinal rats, the i.v. potencies being similar to those of tolperisone and eperisone. These effects of AD-2239 were long-lasting. When orally administered, AD-2239 was 4 times more potent than eperisone. Diazepam was without effect on the extensor reflex in spinal rats. AD-2239 depressed the flexor reflex without affecting the patellar reflex in anesthetized cats. Baclofen depressed the latter. When orally administered, AD-2239, in a dose-related manner, depressed the flexor reflex in anesthetized cats, with a potency approximately 8 times that of tolperisone or eperisone. AD-2239 produced a dose-related reduction of anemic decerebrate rigidity (alpha-rigidity) in rats. The potency, at the minimum effective i.v. dose, was 4 times greater than that of tolperisone or eperisone, equal to that of diazepam, and one-half of that of baclofen. AD-2239 neither affected spontaneous electroencephalogram (EEG) nor EEG arousal response in immobilized cats, while the other drugs, at comparatively low doses, depressed them. The results strongly suggest that AD-2239 may have advantages over the existing centrally acting muscle relaxants in the treatment of human clinical spasticity and muscle spasm syndromes.
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PMID:Pharmacological studies of 1-(2,3-dimethyl-4-methoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1- propanone hydrochloride (AD-2239), a centrally acting muscle relaxant. 383 47

Variations in four electrophysiological tests (H/M, T/M, vibratory inhibition, and recovery curve of Hoffmann's reflex following stimulation at the ankle) were studied following a single administration of four myorelaxant drugs: diazepam (10 mg intramuscularly), baclofen (20 mg intramuscularly), tizanidine (4 mg orally), and idrocilamide (60 mg intramuscularly). Fifty-one spastic patients, divided into four groups, were tested. All four drugs reduced the H/M and T/M ratios very slightly. Only diazepam and tizanidine reinforced vibratory inhibition. Diazepam and tizanidine did not modify the abnormal recovery curves, however, whereas baclofen and idrocilamide did. Reinforcement of vibratory inhibition suggests an increase in presynaptic inhibition mediated by gamma-aminobutyric acid; changes in recovery curves are likely due to modifications of interneuronal reactivity. Matching myorelaxants to the predominant pathophysiological abnormality detected by electrophysiological exploration may lead to better treatment of spasticity.
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PMID:Electrophysiological analysis of the mode of action of muscle relaxants in spasticity. 398 91


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